An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms

Oliver Rocks(Max Planck Institute of Molecular Physiology), Anna Peyker(Max Planck Institute of Molecular Physiology), Martin Kahms(Max Planck Institute of Molecular Physiology), Peter J. Verveer(Max Planck Institute of Molecular Physiology), Carolin Koerner(Max Planck Institute of Molecular Physiology), María Lumbierres(Max Planck Institute of Molecular Physiology), Jürgen Kuhlmann(Max Planck Institute of Molecular Physiology), Herbert Waldmann(Max Planck Institute of Molecular Physiology), Alfred Wittinghofer(Max Planck Institute of Molecular Physiology), Philippe I. H. Bastiaens(Max Planck Institute of Molecular Physiology)
Science
February 10, 2005
10.1126/science.1105654
Cited by 853

Abstract

We show that the specific subcellular distribution of H- and Nras guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the PM via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors.

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